Multiple Sclerosis--the vascular connection

From Rindfliesch's discovery of the central vessel in the MS lesion in 1863, to Dr. Paolo Zamboni's discovery of Chronic Cerebrospinal Venous Insufficiency. 150 years of MS research on blood flow and perfusion of the central nervous system.
Because the heart and the brain are connected.

Welcome! This blog contains research, information on lifestyle, nutrition, dietary supplements and health for those with MS, as well as continuing information on the understanding of CCSVI and cerebral hypoperfusion. This blog is informative only--all medical decisions should be discussed with your own physicians.

The posts are searchable---simply type in your topic of interest in the search box at the top left.

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the immune paradigm of MS, and continues the 15 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.

To learn how this journey began, read my first post from August, 2009. Be well! Joan

Monday, July 27, 2015

We are just beginning to understand the brain's lymphatic vessels, and how this newly discovered system may be implicated in neurodegenerative diseases like MS. It will be important to consider the mechanistic system which enables lymphatic drainage to mature and function. In recent experiments conducted with mice, veins are implicated in lymphatic flow. In fact, when mice had veins that did not drain, but had a reflux of blood flow---like what we see in CCSVI---lymph stopped flowing. And lymph vessels stopped forming correctly, due to endothelial dysfunction.

Flow means "go" for proper lymph system developmentPHILADELPHIA--The lymphatic system provides a slow flow of fluid from our organs and tissues into the bloodstream. It returns fluid and proteins that leak from blood vessels, provides passage for immune and inflammatory cells from the tissues to the blood, and hosts key niches for immune cells. How this system develops hasn't been well understood, but now researchers from the Perelman School of Medicine at the University of Pennsylvania have found from experiments in mice that the early flow of lymph fluid is a critical factor in the development of mature lymphatic vessels. The project was prompted in part by recent studies of cultured lymphatic vessel endothelial cells that suggested that fluid forces could be an important factor in the maturation of lymphatic vessels. But there was no straightforward way to test this hypothesis in live animals.

"No one had been able to come up with a way to stop lymph flow in embryonic animals, without preventing their lymphatic vessels from developing in the first place," said first author Daniel T. Sweet, PhD, a postdoctoral fellow in the Kahn Laboratory.

In humans and other mammals, the lymphatic system is a low-flow system that, unlike the blood circulatory system, has no central pump. Instead it relies on muscular contraction of the mature lymphatic vessel wall and small valves in lymphatic vessels to squeeze fluid along and prevent backflow.

Larger collecting lymphatic vessels receive many small inflows from lymphatic capillaries in surrounding tissues. "You can't just close one of the vessels to block flow downstream--there are many other tributaries coming in," said Sweet.

The solution to testing the role of flow in developing lymphatic vessels turned out to be a line of transgenic mice, developed earlier by the Kahn laboratory. Lacking a gene called Clec2, the mice fail to produce a certain receptor on blood platelets, with a remarkable result: veins that normally help drain the lymph system leak back into it. Like an ocean tide surging into a river, this upstream flow of blood stops the usual downstream flow of lymph.

What's more, the researchers found that smooth muscle cells, which normally form a thin lining in mature lymphatic vessels, and perform contractions that help lymph flow, instead formed an abnormally thick lining, as if the usual signal to shut off cell proliferation were missing.

"We started off thinking that flow might have a role just in valve formation, but ended up realizing that flow is really controlling all aspects of the maturation of these lymphatic vessels," said Sweet.

If flow is essential for a healthy lymphatic cleansing system---which we now know is part of the brain as well as other organs---the lack of venous drainage for the brain and spine could have disaterous affects on immune cells and metabolite cleansing processes. And reflux and slowed flow of venous blood in the jugular veins--as noted in CCSVI--could be shutting down the lymphatic drainage system of the brain. Endothelial dysfunction, which has also been noted in MS, also plays a role in the cessation of lymphatic flow. Flowing fluids create shear stress, and are needed for healthy endothelial cells. It's a virtuous cycle.

Wednesday, July 15, 2015

We have a brand new peer-reviewed paper from the researchers of the ISNVD which is considering the vascular connection to MS. It is called:
"Blood circulating microparticle species in relapsing–remitting and secondary progressive multiple sclerosis. A case–control, cross sectional study with conventional MRI and advanced iron content imaging outcomes" This paper is published in the Journal of Neurological Sciences.http://www.jns-journal.com/article/S0022-510X%2815%2900309-3/abstract

The researchers looked at serum markers of healthy individuals and compared them to people with MS. (Can I just inject a "Hallelujah" here? This was my dream eight years ago, and it is now a reality.) What they found were that in people with MS, there are circulating microparticles in the blood that aren't found in healthy people. These markers (CD31+/CD51+/CD61+/CD54+) are microparticles which are shed from the lining of the damaged endothelium. We see the same markers in cardiovascular disease. These markers are associated with coronary artery disease, hypercoagulation, thrombosis (clotting) and stroke. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2010.04007.x/full

It's been eight years since I first put together research on MS as a disease connected to blood flow and the vascular system. What I saw in Jeff's blood results when he was diagnosed during his first severe flare---hypercoagulation, high c reactive protein, high inflammatory markers---looked to me like a vascular reaction caused by endothelial dysfunction. I sent the research I compiled to university researchers, and created a nutrition and lifestyle program for Jeff, to address this issue. My hope was that he could find stability in his disease process, by reducing the impact of vascular endothelial dysfunction. I saw that cardiovascular researchers, like Dr. John Cooke, were having great success with their heart patients, and that encouraged me! And sure enough, after three months on the Endothelial Health Program, Jeff's serum markers of endothelial dysfunction were lowered, and his MS stayed in remission.

What I saw in Jeff's serum markers was real. Although his neurologist claimed it had "nothing to do with MS"---it appears that wasn't true, and Jeff is not alone. These markers were shown to be correlated with lesions and brain atrophy in MS using SWI and MRI scans.
Here is the conclusion from the researchers: These results indicate that circulating microparticles' profiles in MS may support mechanistic roles for microvascular stress and injury which is an underlying contributor not only to MS initiation and progression, but also to pro-inflammatory responses.

This means that stress and injury to the endothelial lining, also known as endothelial dysfunction, may be a contributor to MS initiation and progression.

The good news is that there are things we can all do today to reduce endothelial dysfunction, cellular stress and injury and bring these serum markers down. The hope is that by helping the endothelium heal, we can limit microparticle shedding into the blood, and reverse this inflammatory process.

What would be the next step? Retest the microparticle levels in pwMS after they have been on the endothelial health program for months/years---and see if this correlates to a slowing or stopping of MS disease progression. If Jeff is any indication, there is great hope.

Talk to your own doctor, see if it might be something you can do. I am not a doctor, so it's always best to consult one before beginning a new regimen! Keep an eye on your blood levels of Crp, hypercoagulation, d-dimer, AST and ALT, and serum cholesterol--as well as vitamin D and B12 levels.

Saturday, June 27, 2015

I write a lot. Today I just wanted to share some images, because these pictures speak loudly and can amplify recent blog posts. Some neurologists are saying there's no way the newly discovered lymphatic vessels and CCSVI are related. But they are wrong. Just as they have been wrong about the brain's "immune privilege" and the EAE mouse model of MS.http://ccsviinms.blogspot.com/2015/06/rewrite-textbooks.html

The following images are all of the venous and lymphatic drainage of the brain, from the back of the head.

This is an MRI picture from the Kipnis Lab at the University of Virginia, of the newly discovered lymphatic vessels, shown with red dye. These were also found in human cadaver tissue. These newly discovered vessels directly follow the path of the brain's draining veins, shown with green dye.

This is an illustration of the veins which drain the human and mammalian brains. Cortical veins at the top of the head lead into the superior sagittal sinus. They branch off on either side, forming the transverse sinus, where they eventually head south into the jugular veins. See how nice and open they appear? Lymph vessels follow this system. Lymph vessels drain lymph carrying immune cells, metabolites, proteins and toxins from the brain into jugular veins. You can see how the mouse brain image above matches this.

The image below shows the location of the cervical lymph nodes. All of the lymph collected in the newly discovered vessels flows alongside the veins and back to the cervical lymph nodes. Notice that they are situated alongside the jugular vein.

AND finally, this is an MRV image of my husband Jeff's brain draining veins. Notice the straight cortical veins, leading down into the transverse sinus, where they branch off. And then....what the what? His sigmoid sinus and jugular foramen are pinched off, creating a mess of curly collaterals beneath. His brain's blood flow and lymph were all slowed to a stall, waiting to be being drained. He was sick, tired, had over 20 cerebral lesions, and had just received an MS diagnosis.

His sigmoid sinus and jugular veins have since been stented, and he now has normalized flow going through his jugular veins. The collaterals disappeared. How has this impacted his brain health? Well, he hasn't had any more MS lesions and his gray matter atrophy reversed. He's running around, always on the go, very thankfully still driving me crazy. Yes, this is all anecdotal. But sigmoid stenting is an approved treatment for intracranial hypertension. It's not vodoo. It improves cerebrospinal fluid and blood flow, and helps people heal. And now we know, this is where lymph flows, as well.

I would contend that this is something SOMEBODY might like to study. All it would take would be to block the mouse veins at the sigmoid sinus, insert the tracer dye into the lymphatic vessels, and watch what happens to the drainage of lymph. I'll bet you it isn't good.

About Me

I became interested in multiple sclerosis (MS) research when my husband Jeff was diagnosed with MS in 2007. I noted a connection of Jeff's disease process to his circulation and blood, and by accessing medical journals on the internet and stacks of books at my local library, I put together research to address this. I sent my theory and research, called the Endothelial Health Program, to universities, and began a correspondence with vascular specialists at Stanford University.
Jeff was the first American treated for CCSVI, and he is now six years past his venoplasty, with no further MS progression, healing of his gray matter, and relief of many symptoms.